Transcript pedigrees and disorders

Pedigrees, karyotypes, and
genetic disorders
CLE 3210.4.4 Compare different modes of
inheritance: sex linkage, co-dominance,
incomplete dominance, multiple alleles, and
polygenic traits.
CLE 3210.4.6 Describe the connection between
mutations and human genetic disorders.
Overview
• Review karyotypes and chromosome type
• Discuss mutations and various genetic
disorders
• Compare these with sex-linked inheritance
• Apply the use of karyotypes and pedigrees
to better understand inheritance
Karyotypes
• A karyotype is an organized profile of an individual’s
chromosomes. In a karyotype, chromosomes are arranged
and numbered by size, from largest to smallest.
• Humans have 46 chromosomes or 23 pairs.
• 22 of these pairs are autosomes.
• 1 pair are sex chromosomes, X and Y.
• Which chromsomes do females have? Males?
3
Normal Karyotype
Autosomes
(44) 
 Sex
chromosomes
(2)
Abnormal Karyotype
Autosomes
(44) 
 Sex
chromosomes
(2)
*3 Chromosomes instead of 2
Images from: http://www.bbc.co.uk/scotland/education/bitesize/higher/img/biology/genetics_adaptation/mutations/02gene_mutation.gif
KINDS OF MUTATIONS
Mutations that produce changes
in a single gene =
GENE MUTATIONS
_________________
Mutations that produce changes
in whole chromosomes =
CHROMOSOMAL
MUTATIONS
_____________________
KINDS OF MUTATIONS
SOMATIC CELLS
BODY
________
CELLS = ___________
Somatic cell mutations can:
______________________
Cause cancer
Make cell not able to function
______________________
_____________
Kill cell
WON’T BE passed on to offspring
BUT _________
Kinds of Mutations
GAMETES
___________
(sperm & eggs)
GERM
= _________cells
CAN BE passed
 Germ cell mutations ________
on to offspring
http://anthro.palomar.edu/biobasis/images/meiosis.gif
MANY HUMAN GENES
HAVE BECOME KNOWN
THROUGH THE STUDY
OF GENETIC DISORDERS
DISORDERS result from
Many genetic ___________
changes in the DNA code so
NON-FUNCTIONING
_________________ proteins are
produced.
http://patentdocs.typepad.com/photos/uncategorized/2007/05/28/dna1.gif
What do I need to know about each
disorder?
• Which specific type of disorder it is:
– Autosomal Recessive
– Autosomal Dominant
– Sex-Linked
– Nondisjunction
– Codominant
• What causes it
• Characteristics of it
Autosomal Recessive Disorders
• A mutation that creates a
disfunctional protein that
appears RECESSIVE to the
working allele.
• Example: Albinism:
• Includes:
– AA = no albinism
–
–
–
–
–
Albinism
Cystic Fibrosis
Phenylketonuria (PKU)
Tay-Sach’s disease
Sickle-cell disease
– Aa = carrier for
albinism
– aa = albino
Autosomal Recessive
Disorders
• Albinism
– Characterized by lack of pigment in the
skin, hair, and eyes.
Albinism
Autosomal recessive: CYSTIC
FIBROSIS
CAUSE:
Loss of 3 DNA bases in a gene for the
_____________
that transports _________
so
protein
Cl- ions
salt balance is upset
thick mucous
Causes a build up of _________________
in lungs
and digestive organs
Image from: BIOLOGY by Miller and Levine; Prentice Hall Publishing ©2006
Phenylketonuria (PKU)
CAUSE:
ENZYME
Mutation in gene for an ___________
that __________
called
breaks down an ___________
amino acid
phenylalanine
X
X
MENTAL RETARDATION
Build up causes ________________________
http://biology.clc.uc.edu/courses/bio104/protein.htm
Phenylketonuria (PKU)
ALL babies are ________
tested
____
for PKU before they
leave the hospital.
Treatment:
LOW in phenylalanine to
Need a diet _____________________
extend life and ______________
mental
PREVENT
retardation
amino acid
If phenylalanine is an _____________,
what type of foods should PKU patients avoid?
PROTEINS !
__________________
TAY-SACHS DISEASE
AUTOSOMAL RECESSIVE
___________________
CAUSE:
Mutation in gene for an ___________
ENZYME that
breaks down a kind of _________in
the
LIPID
developing _________
BRAIN
Build up of lipids in brain cells leads to:
mental retardation, blindness, and DEATH
in early childhood
Found more frequently in people with
Jewish _____________
Mediterranean ______________,
Middle Eastern
_______
ancestry
Image from: http://www.djsfoundation.org/images/Steeler%20pics%20Dylan.jpg
Tay-Sachs
heterozygous person
A __________
who carries a
recessive allele for a
_________
genetic disorder, but
doesn’t show
______________
the
disorder themselves
is called a
CARRIER
_____________
http://www.biochem.arizona.edu/classes/bioc460/spring/rlm/RLM36.1.html
A male who is a heterozygous carrier for an
autosomal recessive disease marries a
homozygous unaffected female. What is the
chance of having an affected child? A child
who is a carrier?
A.
B.
C.
D.
50 %; 50%
0%; 50%
50%; 0%
25%; 50%
20
A mutation that codes for a new protein
whose action masks the normal allele
appears as a ______________
DOMINANT mutation.
AUTOSOMAL DOMINANT
Examples of _________________________
GENETIC DISORDERS:
Huntington’s disease
____________________
Achondroplasia
____________________
HUNTINGTON’S DISEASE
AUTOSOMAL DOMINANT
______________________
CAUSE:
CAG repeats at end of gene
Extra 40-100 ______________
on chromosome 4
more repeats . . . the more __________
severe
The _____________
the symptoms.
http://www.healthsystem.virginia.edu/internet/huntdisease/images/cag.gif
HUNTINGTON’S
Huntington’s brain DISEASE
loss
Causes progressive _____
muscle control
of ________________
and
mental
___________function
1 in 10,000 people in U.S.
have Huntington’s disease
Normal brain
http://www.scielo.br/img/revistas/bjmbr/v39n8/html/6233i01.htm
A person with
Huntington’s disease
50% chance of
has a _____
passing the disorder on to
their offspring.
Problem:
Symptoms of disorder usually don’t show
until ____________
MIDDLE AGE . . .
so you don’t know you have it until
________
AFTER you have had children.
ACHONDROPLASIA
(One kind of Dwarfism)
AUTOSOMAL DOMINANT
CAUSE: ___________________________
gene
1 in 20,000 births
Mother has
achondroplasia
200,000 “little people” worldwide
Father has
diastrophic
displasia, a
recessive disorder
Autosomal Dominant
Disorders
• Achondroplasia
– 99.96% of all the people in the world are
homozygous recessive for this trait (aa).
– Interesting fact: The AA (homozygous
dominant) genotype of this trait is lethal
and will result in a spontaneous abortion
of the fetus.
• The only viable genotype is Aa.
Activity 1: With a partner
• Take 5 minutes and draw a two-circle Venn
Diagram to compare and contrast:
• Autosomal recessive Vs. autosomal
dominant
DISORDERS CAUSED
AUTOSOMAL CODOMINANT ALLELES
BY ____________________
SICKLE CELL DISEASE
____________________
CAUSE:
T changed to A
in gene for
HEMOGLOBIN
__________________
(protein in red blood cells
that carries oxygen in blood)
SICKLE CELL DISEASE
SYMPTOMS:
RED BLOOD CELLS become sickle
_____________
TWO
shaped in persons with ______
ALLELES
sickle cell ________
SICKLE CELL DISEASE
Circulatory problems
Cells stick in capillaries
Loss of blood cells (anemia)
Organ damage (brain,
heart, spleen)
Can lead to DEATH
SICKLE CELL DISEASE
AFRICAN AMERICANS
More common in _________________
1 in 500 = have sickle cell disease
1 in 10 = carriers for allele
MEDITERRANEAN
Also affects persons of _______________
and _________________
MIDDLE EASTERN
descent
Why do so many African Americans
carry the sickle cell allele?
SICKLE CELL DISEASE
Many can trace their ancestry to west
MALARIA
central Africa where ___________,
a serious parasitic disease that
infects red blood cells is common.
Images from: http://en.wikipedia.org/wiki/Malaria
A person who is __________________
for
HOMOZYGOUS
the ____________allele
(ss) will have
sickle cell
_______________
sickle disease
HOMOZYGOUS
A person who is _________________
for
normal hemoglobin alleles will have normal
blood cells, but can become infected with
malaria
__________
(SS)
HETEROZYGOUS person (Ss)
A _________________
(with one normal/one sickle cell allele) is
generally healthy and has the benefit of
resistant to malaria
being _________
Chromosomes that determine
the sex of an organism =
_________________
Sex chromosomes
http://www.angelbabygifts.com/
All other chromosomes =
_________________
autosomes
Humans have two sex chromosomes
X
y
and _____
44 autosomes
SEX DETERMINATION
XX = female
Xy = male
Who decides?
Mom can give X
Dad can give
X or y
X
X
X
XX
XX
y
Xy
Xy
Dad determines sex of the baby.
SO ____
If dad gives X with mom’s X = girl
If dad give y with mom’s X = boy
Sex linked genes
• In addition to their role in
determining sex of an organism, X
and Y chromosomes have many
other genes that are unrelated to
sex.
• A gene on either sex chromosome
is call a sex-linked gene.
• Congenital generalized
hypertrichosis (CGH), the type that
Danny Gomez has, is X-linked
dominant; the gene that is
mutated is found on the X
chromosome.
• Sex-linked mutations can be either
dominant or recessive.
X-linked inheritance
pattern from a
heterozygote mother and
unaffected father 37
PEDIGREES
_______________are
diagrams
genes are passed
that show how are ____________
in families
on __________
over several
generations
Drawing a pedigree chart
http://www.beavton.k12.or.us/sunset/academics/genetics.htm
Genes carried on X or Y
chromsomes=
___________________
SEX LINKED TRAITS
These traits show up in different
_______________
in males and females
percentages
because they move with the sex
chromosomes
Y-LINKED GENES:
carried on Y
Genes ______________
chromosome
EXAMPLE:
Hairy pinna
ONLY show up _______
in males
Y linked
_________genes
_____
X-LINKED GENES:
____________
are carried on the X chromosome
X-linked recessive disorders
MORE frequently
show up _____________
in MALES
______ than females
because males only have
ONE X chromosome.
______
Males ONLY HAVE ONE X
DEFECTIVE
They either
have the
disorder
NORMAL
Or
They are
normal
FEMALES HAVE TWO X CHROMOSOMES
DEFECTIVE
NORMAL
DEFECTIVE
Females have
one normal
gene that works.
need 2
Females __________
defective recessive
alleles to show the
disorder
X-LINKED RECESSIVE
Examples of ________________________
DISORDERS:
HEMOPHILIA
____________________
COLORBLINDNESS
____________________
DUCHENNE MUSCULAR DYSTROPHY
____________________
HEMOPHILIA
CAUSE:
Mutation in genes for __________________
Blood clotting proteins
on X chromosome
carried ______
Blood clotting proteins are missing so person
with this disorder can’t stop bleeding when
bleed to death from minor
injured; can ________________
cuts or suffer internal bleeding
from bruises or bumps.
COLORBLINDNESS
CAUSE:
Mutation in one of three genes for
_______________
carried on X chromosome
Color vision
Persons with this disorder have trouble
distinguishing colors.
Red-green
_________________
colorblindness is most common
Seen in 1 in 10 males
1 in 100 females
http://gizmodo.com/gadgets/peripherals/samsung-develops-lcd-for-colorblind-036306.php
Duchenne Muscular Dystrophy
CAUSE:
deletion in gene
that codes for a
muscle protein
_______________
Results in
progressive weakening
____________________
and loss of
skeletal
muscle
___________________
http://www.cadenhead.org/workbench/gems/jerry-lewis-telethon.jpg
http://www.tokyo-med.ac.jp/genet/chm/dei.gif
What’s the pattern:
Y-linked traits show up _______
ONLY in _______
males
________
X-linked recessive traits:
__________________
______________________
more common in males than females.
________________
ONLY FEMALES can be ________.
carriers
AUTOSOMAL RECESSIVE traits:
_______________________
FEMALES can be ________
carriers
BOTH MALES
______ & _________
Activity 2 (group): Interpreting
pedigrees
• Using your pedigree reference sheet, try to
identify the inheritance pattern for each
pedigree on the handout.
• Is it:
– Sex-linked dominant?
– Autosomal dominant?
– Autosomal recessive?
CHROMOSOMAL MUTATIONS
____________________________:
structure or
Change in the ______________
number
____________
of chromosomes
Homologous chromosomes
fail to separate during MEIOSIS
________________
NONDISJUNCTION
= _________________________
One cell gets 2 copies of
the chromosome the
other cell gets none.
Normal Meiosis
Nondisjunction
http://web.udl.es/usuaris/e4650869/docencia/gen_etica/meioferti2.html
http://www.tokyo-med.ac.jp/genet/anm/domov.gif
Human Abnormalities
caused by Non-Disjunction
__________________
Down syndrome
Klinefelter syndrome
__________________
Turner syndrome
__________________
TRISOMY 21
Down syndrome (= ____________)
Non-Disjunction Disorders
• Down Syndrome (1:700)
– Characterized by obvious physical features
and mild to profound mental disabilities.
• Short stature, heart defects, short lifespan,
often sexually underdeveloped and sterile.
– Caused by a duplication of the 21st
chromosome (47 TOTAL) = TRISOMY 21.
Turner syndrome – “monosomy”
Non-Disjunction Disorders
• Turner’s Syndrome (1:5,000)
– THIS SYNDROME IS THE ONLY VIABLE
MONOSOMY WHICH EXISTS IN HUMANS.
• 98% of these fetuses die prior to birth
– Individuals affected with this disorder develop
as females only.
– Occurs when all or part of one of the X
chromosomes is missing (45 TOTAL)
=MONOSOMY X.
– Characterized by short stature, webbed neck,
stocky build and absence of sexual
development; normal intelligence.
Klinefelter syndrome XXy
Non-Disjunction Disorders
• Klinefelter’s Syndrome
– A condition which occurs in males only.
– Individuals with this disorder have an extra
X sex chromosome (47 TOTAL) = TRISOMY
XXY.
– This disorder can affect the stages of
language, physical, and social development.
– Characteristics include small testes, breast
enlargement and other feminine body
attributes; normal intelligence.
Which disorder is this?
Which disorder is this?
Which disorder is this?
Polygenic traits – Eye color
Compare and contrast
•
•
•
•
Complete dominance
Incomplete dominance
Co-dominance
Sex-linked